Background: Live attenuated influenza vaccine (LAIV) was found to be safe and effective in children for preventing influenza, but an increased risk for medically attended asthma visits was observed in a post licensure study in young children, so the manufacturer did not seek an initial indication in children <5 years of age. It has been hypothesized that the risk of asthma from LAIV is greatest in the very young, and that the risk diminishes with age.

Methods: We recovered patient identifiers from the original placebo-controlled LAIV study and determined which enrollees received vaccine vs. placebo. Our study focused on members 3 years and younger at the time of initial immunization. We then followed each person’s medical utilization over a 14 year period after immunization, and noted all visits for asthma for each year of age in which the child was a health plan member for the entire year. For each year of age, we compared the two arms of the trial with respect to the proportion of children with any asthma diagnosis during the year. The proportions with asthma were plotted by vaccine (LAIV v placebo) and year of age. The effect of LAIV on risk of asthma over time were further examined using logistic regression with repeated measures (accounting for the correlated yearly asthma outcomes).

Results: We included 1151 children 1-2 years old out of the original 1154 of the study. All children were randomized 2:1 to receive 2 doses of same treatment: 762 ( 66.2% ) received LAIV, and 389 (33.8% ) received placebo. 2/3 of the study population were still members in 2014, and there was no evidence of differential drop-out by treatment group. Time to first diagnosis was not statistically different between the vaccine and placebo groups, and the hazard ratio for asthma diagnosis in patients with LAIV was 1.112 (95% Confidence Interval 0.877-1.409).

Conclusion: We found no evidence of an increased risk of asthma over a 14 year period, in children who received LAIV before the age of three, compared with placebo.